4jai

Publication Abstract from PubMed

Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2. Furthermore, this compound inhibited phosphorylation of histone H3 (pHH3) in mouse bone morrow upon oral administration, which is consistent with inhibition of Aurora kinase B activity.

SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors.,Karra S, Xiao Y, Chen X, Liu-Bujalski L, Huck B, Sutton A, Goutopoulos A, Askew B, Josephson K, Jiang X, Shutes A, Shankar V, Noonan T, Garcia-Berrios G, Dong R, Dhanabal M, Tian H, Wang Z, Clark A, Goodstal S Bioorg Med Chem Lett. 2013 May 15;23(10):3081-7. doi: 10.1016/j.bmcl.2013.03.008., Epub 2013 Mar 13. PMID:23570792^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.